Dataset Information

Effect of Peptide Receptor Radionuclide Therapy in Combination with Temozolomide against Tumor Angiogenesis in a Glioblastoma Model.

ABSTRACT: Cell adhesion receptor integrin αvβ3 is a promising biomarker for developing tumor-angiogenesis targeted theranostics. In this study, we aimed to examine the therapeutic potential of peptide receptor radionuclide therapy (PRRT) with 188Re-IDA-D-[c(RGDfK)]2 (11.1 MBq). The results showed that the tumor volume was significantly decreased by 81% compared with the vehicle-treated group in U87-MG xenografts. The quantitative in vivo anti-angiogenic responses of PRRT were obtained using 99mTc-IDA-D-[c(RGDfK)]2 SPECT and corresponded to the measured tumor volume. PRRT combined with temozolomide (TMZ) resulted in a 93% reduction in tumor volume, which was markedly greater than that of each agent used individually. In addition, histopathological characterization showed that PRRT combined with TMZ was superior to PRRT or TMZ alone, even when TMZ was used at half dose. Overall, our results indicated that integrin-targeted PRRT and TMZ combined therapy might be a new medical tool for the effective treatment of glioblastoma.

SUBMITTER: Lee SH

PROVIDER: S-EPMC8507696 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Peptide Receptor Radionuclide Therapy in Combination with Temozolomide against Tumor Angiogenesis in a Glioblastoma Model.

Lee Sang Hee SH Choi Ji Young JY Jung Jae Ho JH Song In Ho IH Park Hyun Soo HS Denora Nunzio N Leonetti Francesco F Kim Sang Eun SE Lee Byung Chul BC

Cancers 20211008 19

Cell adhesion receptor integrin αvβ3 is a promising biomarker for developing tumor-angiogenesis targeted theranostics. In this study, we aimed to examine the therapeutic potential of peptide receptor radionuclide therapy (PRRT) with 188Re-IDA-D-[c(RGDfK)]2 (11.1 MBq). The results showed that the tumor volume was significantly decreased by 81% compared with the vehicle-treated group in U87-MG xenografts. The quantitative in vivo anti-angiogenic response ...[more]

PMID: 34638512

Similar Datasets

Project description:Pretherapy PET with 86Y-DOTATOC is considered the ideal dosimetry protocol for 90Y-DOTATOC therapy; however, its cost, limited availability, and need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. The goal of this study was to develop a dosimetric method for 90Y-DOTATOC using 90Y-DOTATOC PET/CT and bremsstrahlung SPECT/CT and to determine whether dosimetry-based administered activities differ significantly from standard administered activities. Methods: This was a prospective phase 2 trial of 90Y-DOTATOC therapy in patients with somatostatin receptor-positive tumors. 90Y-DOTATOC was given in 3 cycles 6-8 wk apart. In the first cycle of therapy, adults received 4.4 GBq and children received 1.85 GBq/m2; the subsequent administered activities were adjusted according to the dosimetry of the preceding cycle so as not to exceed a total kidney dose of 23 Gy and bone marrow dose of 2 Gy. The radiation dose to the kidneys was determined from serial imaging sessions consisting of time-of-flight 90Y-DOTATOC PET/CT at 5 h after therapy and 90Y-DOTATOC bremsstrahlung SPECT/CT at 6, 24, 48, and 72 h. The PET/CT data were used to measure the absolute concentration of 90Y-DOTATOC and to calibrate the bremsstrahlung SPECT kidney clearance data. The radiation dose to the kidneys was determined by multiplying the time-integrated activity (from the fitted biexponential curve of renal clearance of 90Y-DOTATOC) with the energy emitted per decay, divided by the mass of the kidneys. Results: The radiation dose to the kidneys per cycle of 90Y-DOTATOC therapy was highly variable among patients, ranging from 0.32 to 3.0 mGy/MBq. In 17 (85%) of the 20 adult patients who received the second and the third treatment cycles of 90Y-DOTATOC, the administered activity was modified by at least 20% from the starting administered activity. Conclusion: Renal dosimetry of 90Y-DOTATOC is feasible using 90Y-DOTATOC time-of-flight PET/CT and bremsstrahlung SPECT/CT and has a significant impact on the administered activity in treatment cycles.

Project description:IntroductionClinical experiences of peptide receptor radionuclide therapy (PRRT) in patients with adrenocorticotropic hormone (ACTH) producing neuroendocrine tumor (NET) were extremely rare.Case presentationA 60-year-old woman with hypertension, lower-extremity edema, hypoalbuminemia, hypokalemia, and multiple hepatic tumors was hospitalized for further examination and treatment. Endocrine testing detected excessive levels of ACTH and cortisol in her blood. Pathohistological examination revealed the hepatic lesions to be ACTH-positive grade 2 NETs (G2). A diagnosis of ectopic ACTH-producing NET was made. The patient was initially treated with the 11-hydroxylase inhibitor, metyrapone, to control hypercortisolemia and the long-acting somatostatin analog, lanreotide. Simultaneously, everolimus was continued for about 1 year. Subsequently, hepatic tumors were surgically resected, leading to successful and rapid normalization of ACTH secretion and resolution of hypercortisolemia. However, the disease relapsed and presented with multiple hepatic masses and increased ACTH 18 months after surgery. As sunitinib and subsequent streptozocin chemotherapy failed to control the disease, PRRT with 177Lu-DOTATATE was performed. ACTH levels increased after initiation of PRRT, and clinical manifestations, such as pigmentation, hypertension, and hyperglycemia, were remarkable. The patient was treated with antihypertensive and antidiabetic agents, and required an increased dose of metyrapone and addition of the cortisol biosynthesis inhibitor, osilodrostat. After four cycles of PRRT, the hepatic tumors showed a remarkable reduction in size with normalization of ACTH level and withdrawal of cortisol synthesis inhibitors.ConclusionAlthough PRRT was effective, we should consider the occurrence of hormonal crisis during the therapy. Due to the rarity and complexity of hormone-producing tumors, cooperation between medical oncologists and endocrinologists is important for patient management.

Dataset Information

Effect of Peptide Receptor Radionuclide Therapy in Combination with Temozolomide against Tumor Angiogenesis in a Glioblastoma Model.

Publications

Effect of Peptide Receptor Radionuclide Therapy in Combination with Temozolomide against Tumor Angiogenesis in a Glioblastoma Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets